Fungicides

ABSTRACT

This invention relates to derivatives of acrylic acid of the formula: ##STR1## useful as fungicides, to processes for preparing them, to fungicidal compositions containing them, and to methods of using them to combat fungi, especially fungal infections in plants. The values of the variables are provided herein.

This invention relates to derivatives of acrylic acid useful asfungicides, to processes for preparing them, to fungicidal compositionscontaining them, and to methods of using them to combat fungi,especially fungal infections in plants.

The invention provides a compound having the general formula (I):##STR2## and stereoisomers thereof, wherein X, Y and Z, which are thesame or different, are hydrogen, halogen, hydroxy, optionallysubstituted alkyl, optionally substituted alkenyl, optionallysubstituted aryl, optionally substituted alkynyl, optionally substitutedalkoxy, optionally substituted aryloxy, optionally substituted aralkyl,optionally substituted arylalkoxy, optionally substituted aryloxyalkyl,optionally substituted acyloxy, optionally substituted amino, acylamino,cyano, nitrile, --CO₂ R¹, --CONR² R³, or --COR⁴, or X and Y, when theyare in adjacent positions on the phenyl ring, join to form a fused ring,either aromatic or aliphatic, optionally containing one or moreheteroatoms; W is a C-linked optionally substituted six memberedheterocyclic ring other than pyrimidinyl, containing two to fournitrogen atoms, and wherein adjacent substituents may together form afused aromatic or hetero-aromatic ring; A is oxygen or sulphur; and R¹,R², R³, and R⁴, which are the same or different, are hydrogen, alkyl,cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, optionally substitutedaryl or optionally substituted aralkyl; and metal complexes thereof.

The compounds of the invention contain at least one carbon-carbon doublebond, and are sometimes obtained in the form of mixtues of geometricisomers. However, these mixtures can be separated into individualisomers, and this invention embraces such isomers and mixtures thereofin all proportions including those which consist substantially of the(E)-isomer and those which consist substantially of the (Z)-isomer.

The individual stereoisomers which result from the unsymmetricallysubstituted double bond of the acrylate group are identified by thecommonly used terms "(E)" and "(Z)". These terms are defined accordingto the Cahn-Ingold-Prelog system which is fully described in theliterature (see, for example, J March, "Advanced Organic Chemistry," 3rdedition, Wiley-Interscience, page 109 et seq).

Usually one isomer is more fungicidally active than the other; the moreactive isomer being the one in which the group --OCH₃ is on the sameside of the double bond as the substituted phenyl ring. In the case ofthe compounds of the present invetion this is the (E)-isomer. Theseisomers form a preferred embodiment of the invention.

The formula: ##STR3## used hereinafter signifies a separable mixture ofboth geometric isomers about the acrylate double bond, i.e. ##STR4##

Alkyl, wherever present as a group or moiety (in, for example, "alkoxy"and "aralkyl") can be in the form of straight or branched chains, andpreferably contains 1 to 6, more preferably 1 to 4, carbon atoms;examples are methyl, ethyl, propyl, (n- or iso-propyl) and butyl (n-,sec-, iso- or t-butyl). Optional substituents of alkyl include hydroxy,halogen (especially chlorine and fluorine), C₁₋₄ alkoxy and C₁₋₄alkoxycarbonyl.

Preferred substituent haloalkyl groups are halo-(C₁₋₄) alkyl groups andthe same applies for preferred haloalkoxy groups. Of particular interestare trifluoromethyl and trifluoromethoxy. Cycloalkyl is preferably C₃₋₆cycloalkyl and includes cyclohexyl. Cycloalkylalkyl is preferably C₃₋₆cycloalkyl (C₁₋₄)alkyl, for example, cyclopropylethyl.

Aralkyl itself and the aralkyl moiety of arylalkoxy include,particularly, phenylalkyl (especially benzyl, phenylethyl, phenylpropyl,phenylbutyl or phenylhexyl) in which the alkyl moiety may carry othersubstituents such as hydroxy or C₁₋₄ alkoxy and the aryl moiety may besubstituted with, for example, one or more of halogen (especiallychlorine or fluorine), hydroxy, C₁₋₄ alkyl (especially methyl), C₁₋₄alkoxy (especially methoxy), trifluoromethyl, trifluoromethoxy,optionally substituted phenoxy, optionally substituted benzyloxy, nitro,amino, phenyl, carboxy or a carboxylic acid ester, cyano,alkylcarbonylamino and methylenedioxy. Substituents which may be presenton the phenoxy and benzyloxy groups include any of those othersubstituents which may be present on the aryl moiety of aralkyl.

Aryloxyalkyl includes, in particular, phenoxyalkyl (especiallyphenoxymethyl and phenoxyethyl) in which the alkyl moiety may carryother substituents such as methoxy and the aryl moiety may besubstituted in the same way as the aryl moiety in aralkyl above.

Alkenyl and alkynyl groups preferably contain 2 to 6 carbon atoms and,more preferably, 2 to 4 carbon atoms in the form of straight or branchedchains. Ethenyl, propenyl and butenyl are examples of alkenyl groups.Optional substituents or alkenyl include aromatic and heteroaromaticgroups (such as phenyl, furyl, thienyl and pyridyl) which may themselvescarry substituents such as those described for the aryl moiety ofaralkyl above. These include halogen (especially chlorine or fluorine).Further, the terminal carbon atom of the alkenyl groups may form part ofa 5- or 6-membered cycloalkyl ring. Alkynyl includes ethynyl and isoptionally substituted by, for example, phenyl which may itself besubstituted as for the aryl moiety of aralkyl above.

Aryl itself and the aryl moiety of aryloxy are preferably phenyl. Theymay be substituted in the same way as the aryl moiety of aralkyl above.

Optional substituents which may be carried by an amino group include oneor two of N-aryl and N-alkyl groups (such as N-phenyl or N-methyl).

Acyl itself and the acyl moiety of acyloxy include, in particular,acetyl and benzoyl in which the benzene ring may be substituted in thesame way as the aryl moiety in aralkyl above. Acylamino includesbenzoylamino, furoylamino and thienylcarbonylamino optionallysubstituted by, for example, N-alkyl (especially N-methyl).

Heterocyclic groups which W may be include pyrazinyl, benzopyrazin-2-yl,pyridazin-3-yl, pyridazin-4-yl, cinnolin-3-yl, cinnolin-4-yl,1,2,3-triazin-4-yl, 1,2,3-triazin-5-yl, 1,2,4-triazin-3-yl,1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,3,5-triazinyl,1,2,4-benzotriazin-3-yl and 1,2,4,5-tetrazinyl.

The foregoing may bear one or more ring substituents or, in the case ofa fused ring system may bear one or more substituents on either, orboth, rings. Examples of such substituents are halogen, nitro, C₁₋₄alkyl optionally substituted with hydroxy or C₁₋₄ alkoxy, C₁₋₄ alkoxy,optionally substituted with halogen, hydroxy or C₁₋₄ alkoxy, phenoxy,optionally substituted with halogen, hydroxy, amino, optionallysubstituted with C₁₋₄ alkyl, or cyano.

Values of W of particular interest are pyrazinyl and 1,3,5-triazinyloptionally substituted as indicated above. Typical substituents arechlorine, bromine, methyl, methoxy and nitro attached to any of the ringcarbon atoms.

With all values of W it is preferred that X, Y and Z, which are the sameor different, are single atoms or sterically small groups such asfluoro, chloro, bromo, hydroxy, methyl, methoxy, trifluoromethyl,methylamino or dimethylamino but are more preferably hydrogen.

A is preferably oxygen.

The invention is illustrated by the compounds presented in Table Ibelow.

                                      TABLE I                                     __________________________________________________________________________     ##STR5##                                                                                                 Melting                                           Compound                    Point                                             No.   W          A X    Y Z (°C.)                                                                       Olefinic*                                                                          Isomer.sup.+                            __________________________________________________________________________           ##STR6##  O H    H H            .sub.--E                               2                                                                                    ##STR7##  O H    H H Oil  7.50  .sub.--E                               3                                                                                    ##STR8##  O H    H H            .sub.-- E                              4                                                                                    ##STR9##  O H    H H            .sub.--E                               5                                                                                    ##STR10## O H    H H            .sub.--E                               6                                                                                    ##STR11## O H    H H            .sub.--E                               7                                                                                    ##STR12## O H    H H            .sub.--E                               8                                                                                    ##STR13## O H    H H            .sub.--E                               9                                                                                    ##STR14## O H    H H            .sub.--E                               10                                                                                   ##STR15## O H    H H            .sub.--E                               11                                                                                   ##STR16## O H    H H            .sub.--E                               12                                                                                   ##STR17## O H    H H            .sub.--E                               13                                                                                   ##STR18## O H    H H            .sub.--E                               14                                                                                   ##STR19## O H    H H            .sub.--E                               15                                                                                   ##STR20## O H    H H            .sub.--E                               16                                                                                   ##STR21## O H    H H            .sub.--E                               17                                                                                   ##STR22## O H    H H            .sub.--E                               18                                                                                   ##STR23## O H    H H            .sub.--E                               19                                                                                   ##STR24## O H    H H            .sub.--E                               20                                                                                   ##STR25## O H    H H            .sub.--E                               21                                                                                   ##STR26## O H    H H            .sub.--E                               22                                                                                   ##STR27## O H    H H            .sub.--E                               23                                                                                   ##STR28## O H    H H            .sub.--E                               24                                                                                   ##STR29## O H    H H            .sub.--E                               25                                                                                   ##STR30## O H    H H            .sub.--E                               26                                                                                   ##STR31## O H    H H            .sub.--E                               27                                                                                   ##STR32## O H    H H            .sub.--E                               28                                                                                   ##STR33## O H    H H            .sub.--E                               29                                                                                   ##STR34## O H    H H 141-142.5                                                                          7.46  .sub.--E                               30                                                                                   ##STR35## O H    H H            .sub.--E                               31                                                                                   ##STR36## O H    H H            .sub.--E                               32                                                                                   ##STR37## O H    H H            .sub.--E                               33                                                                                   ##STR38## S H    H H            .sub.--E                               34                                                                                   ##STR39## S H    H H            .sub.--E                               35                                                                                   ##STR40## S H    H H            .sub.--E                               36                                                                                   ##STR41## S H    H H            .sub.--E                               37                                                                                   ##STR42## S H    H H            .sub.--E                               38                                                                                   ##STR43## S H    H H            .sub.--E                               39                                                                                   ##STR44## S H    H H            .sub.--E                               40                                                                                   ##STR45## S H    H H            .sub.--E                               41                                                                                   ##STR46## S H    H H            .sub.--E                               42                                                                                   ##STR47## S H    H H            .sub.--E                               43                                                                                   ##STR48## S H    H H            .sub.--E                               44                                                                                   ##STR49## S H    H H            .sub.--E                               45                                                                                   ##STR50## S H    H H            .sub.--E                               46                                                                                   ##STR51## S H    H H            .sub.--E                               47                                                                                   ##STR52## S H    H H            .sub.--E                               48                                                                                   ##STR53## S H    H H            .sub.--E                               49                                                                                   ##STR54## S H    H H            .sub.--E                               50                                                                                   ##STR55## S H    H H            .sub.--E                               51                                                                                   ##STR56## S H    H H            .sub.--E                               52                                                                                   ##STR57## S H    H H            .sub.--E                               53                                                                                   ##STR58## S H    H H            .sub.--E                               54                                                                                   ##STR59## S H    H H            .sub.--E                               55                                                                                   ##STR60## S H    H H            .sub.--E                               56                                                                                   ##STR61## S H    H H            .sub.--E                               57                                                                                   ##STR62## S H    H H            .sub.--E                               58                                                                                   ##STR63## S H    H H            .sub.--E                               59                                                                                   ##STR64## S H    H H            .sub.--E                               60                                                                                   ##STR65## S H    H H            .sub.--E                               61                                                                                   ##STR66## S H    H H            .sub.--E                               62                                                                                   ##STR67## S H    H H            .sub.--E                               63                                                                                   ##STR68## S H    H H            .sub.--E                               64                                                                                   ##STR69## S H    H H            .sub.--E                               65                                                                                   ##STR70## O 3-Cl H H            .sub.--E                               66                                                                                   ##STR71## O 5-Cl H H            .sub.--E                               67                                                                                   ##STR72## O 4-F  H H            .sub.--E                               68                                                                                   ##STR73## O 6-F  H H            .sub.--E                               69                                                                                   ##STR74## S 4-CH.sub.3                                                                         H H            .sub.--E                               70                                                                                   ##STR75## S 4-CH.sub.3 O                                                                       H H            .sub.--E                               71                                                                                   ##STR76## S 4-NO.sub.2                                                                         H H            .sub.--E                               72                                                                                   ##STR77## O H    H H 121-123                                                                            7.45  .sub.--E                               __________________________________________________________________________     *Chemical shift of singlet from olefinic proton on betamethoxyacrylate        group (ppm from tetramethylsilane). Solvent CDCl.sub.3.                       .sup.+ Geometry of betamethoxyacrylate.                                  

The compounds of the invention having the general formula (I) can beprepared from substituted phenols or thiophenols of general formula(VII) by the steps shown in Scheme I. Throughout Scheme I the terms A,X, Y, Z and W are as defined above, and L is a halogen atom or anothergood leaving group.

Thus, compounds of general formula (I), which exist as geometric isomerswhich may be separated by chromatography, fractional crystallisation ordistillation, can be prepared by O-methylation of compounds of generalformula (III) using a base (such as potassium carbonate) and amethylating agent CH₃ --L (II) in a suitable solvent (such asN,N-dimethylformamide) (Step (a) of Scheme I).

Compounds of general formula (III) can be prepared by treatingphenylacetates of general formula (IV) with a base (such as sodiumhydride) and a formic ester (such as methyl formate) in a suitablesolvent (such as N,N-dimethyl formamide) (Step (b) of Scheme I).

Alternatively, compounds of general formula (I) can be prepared fromacetals of general formula (XIII) by elimination of methanol undereither acidic or basic conditions, at a suitable temperature and oftenin a suitable solvent (step (c) of Scheme I). Examples of reagents orreagent mixtures which can be used for this transformation are lithiumdi-isopropylamide; potassium hydrogen sulphate (see, for example, TYamada, H Hagiwara and H Uda, J. Chem. Soc., Chemical Communications,1980, 838, and reference therein); and triethylamine, often in thepresence of a Lewis acid such as titanium tetrachloride (see, forexample, K Nsunda and L. Heresi, J. Chem. Soc., Chemical Communications,1985, 1000).

Acetals of general formula (XIII) can be prepared by treatment of methylsilyl ketene acetals of general formula (XIV) wherein R is an alkylgroup with trimethyl orthoformate in the presence of Lewis acid such astitanium tetrachloride, at a suitable temperature and in a suitablesolvent (see, for example, K Saigo, M Osaki and T Mukaiyama, ChemistryLetters, 1976, 769).

Methyl silyl ketene acetals of general formula (XIV) can be preparedfrom esters of general formula (IV) by treatment with a base and atrialkylsilyl halide of general formula R₃ SiCl or R₃ SiBr, such astrimethylsilyl chloride, or a base and a trialkylsilyl triflate ofgeneral formula R₃ Si--OSO₂ CF₃, in a suitable solvent and at a suitabletemperature (see, for example, C Ainsworth, F Chen and Y Kuo, J.Organometallic Chemistry, 1972, 46, 59).

It is not always necessary to isolate the intermediates (XIII) and(XIV); under appropriate conditions, compounds of genral formula (I) maybe prepared from esters of general formula (IV) in "one pot" by thesuccessive addition of suitable reagents listed above.

Compounds of general formula (IV) can be prepared by esterification ofcompounds of general formula (V) by standard methods described in thechemical literature (Step (d) of Scheme I).

Compounds of general formula (V) can be prepared by the reaction ofcompounds of general formula (VII) with compounds of formula (VI) in thepresence of a base (such as potassium carbonate) and, if necessary, atransition metal or transition metal salt catalyst (such ascopperbronze) in a convenient solvent (such as N,N-dimethylformamide)(Step (e) of Scheme I).

Alternatively, compounds of general formula (IV) can be prepared fromesters of general formula (VIII) by reaction with compounds of generalformula (VI) in the presence of a base (such as potassium carbonate)and, if necessary, a transition metal or transition metal salt catalyst(such as copper-bronze) in a convenient solvent (such asN,N-dimethylformamide) (Step (f) of Scheme I).

Esters of general formula (VIII) can be prepared by esterification ofcompounds of general formula (VII) by standard methods described in thechemical literature (Step (g) of Scheme I).

Compounds of general formula (VII) can be prepared by standard methodsdescribed in the chemical literature. (For example, see, A. Clesse, W.Haefliger, D. Hauser, H. U. Gubler, B. Dewald and M. Baggiolini, J. Med.Chem., 1981, 24, 1465).

Alternatively, compounds of the invention having the general formula (I)can be prepared from phenylacetates of general formula (XII) by thesteps shown in Scheme II. Throughout Scheme II the terms A, W, X, Y, Zand L are as defined above, and m is a protecting group for a phenol orthiophenol group.

Thus compounds of general formula (I) can be prepared by reaction ofcompounds of general formula (IX) with compounds of general formula (VI)in the presence of a base (such as potassium carbonate) and, ifnecessary, a transition metal or transition metal salt catalyst in aconvenient solvent (such as N,N-dimethylformamide) (step (h) of SchemeII).

Compounds of general formula (IX) can be prepared from protected phenolor thiophenol derivatives of general formula (X) by standarddeprotection procedures as set out in the chemical literature (step (i)of Scheme II). For example, phenols of general formula (IX, A═O) can beprepared from benzyl ethers of general formula (X, A═O, M═CH₂ Ph) byhydrogenolysis in the presence of a suitable catalyst (such as palladiumsupported on carbon).

Compounds of general formula (X), in which the group M is a standardphenol or thiophenol protecting group (such as benzyl), can be preparedby O-methylation of compounds of general formula (XI) using a base (suchas potassium carbonate) and a methylating agent CH₃ --L (II) in asuitable solvent (such as N,N-dimethylformamide) (step (j) of SchemeII).

Compounds of general formula (XI) can be prepared by treatingphenylacetates of general formula (XII) with a base (such as sodiumhydride) and a formic ester (such as methyl formate) in a suitablesolvent (such as N,N-dimethylformamide) (step (k) of Scheme II).

Compounds of general formula (XII) can be prepared from compounds ofgeneral formula (VIII) by standard methods described in the chemicalliterature.

In further aspects the invention provides processes as herein describedfor preparing compounds of formula (I). It also provides theintermediate chemicals of formulae (III)-(V), (XIII) and (XIV).##STR78##

The compounds are active fungicides, and may be used to control one ormore of the following pathogens:

Pyricularia oryzae on rice.

Puccinia recondita, Puccinia striiformis and other rusts on wheat,Puccinia hordei, Puccinia striiformis and other rusts on barley, andrusts on other hosts e.g. coffee, pears, apples, peanuts, vegetables andornamental plants.

Erysiphe graminis (powdery mildew) on barley and wheat and other powderymildews on various hosts such as Sphaerotheca macularis on hops,Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaeraleucotricha on apples and Uncinula necator on vines.

Helminthosporium spp., Rhynchosporium spp., Septoria spp. andPseudocercosporella herpotrichoides.

Cercospora arachidicola and Cercosporidium personata on peanuts andother Cercospora species on other hosts for example sugar beet, bananas,soya beans and rice.

Alternari species on vegetables (e.g. cucumber) oil, seed rape, apples,tomatoes and other hosts.

Venturia inaequalis (scab) on apples.

Plasmopara viticola on vines.

Other downy mildews such as bremia lactucae on lettuce, Peronospora spp.on soybeans, tobacco, onions and other hosts and Pseudoperonosporahumuli on hops and Pseudoperonospora cubensis on cucurbits. Phytophthorainfestans on potatoes and tomatoes and other Phytophthora spp. onvegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoaand other hosts.

Some of the compounds have also shown a broad range of activitiesagainst fungi in vitro. They may have activity against variouspost-harvest pathogens of fruit (e.g. Penicillium digitatum and italicumand Trichoderma viride on oranges, Gloeosporium musarum on bananas andBotrytis cinerea on grapes).

Further some of the compounds may beactive as seed dressings againstFusarium spp., Septoria spp., Tilletia spp., (bunt, a seed borne diseaseof wheat), Ustilago spp., Helminthosporium spp. on cereals, Rhizoctoniasolani on cotton and Pyricularia oryzae on rice.

The compounds can move acropetally in the plant tissue. Moreover, thecompouns may be volatile enough to be active in the vapour phase againstfungi on the plant.

The invention therefore provides a method of combating fungi, whichcomprises applying to a plant, to seed of a plant, or to the locus ofthe plant or seed, an effective amount of a compound of general formula(I) as hereinbefore defined, or a composition containing the same.

The compounds may also be useful as industrial (as opposed toagricultural) fungicides, e.g. in the prevention of fungal attack onwood, hides, leather and especially paint films.

The compounds may be used directly but are more conveniently formulatedinto compositions using a carrier or diluent. The invention thusprovides a fungicidal composition comprising a compound of generalformula (I) as hereinbefore defined, and a fungicidally acceptablecarrier or diluent therefor.

The compounds, can be applied in a number of ways. For example they canbe applied, formulated or unformulated, directly to the foliage of aplant, to seeds or to other medium in which plants are growing or are tobe planted, or they can be sprayed on, dusted on or applied as a creamor paste formulation, or they can be applied as a vapour or as slowrelease granules. Application can be to any part of the plant includingthe foliage, stems, branches or roots, or to soil surrounding the roots,or to the seed before it is planted; or to the soil generally, to paddywater or to hydoponic culture systems. The invention compounds may alsobe injected into plants or sprayed onto vegetation using electrodynamicspraying techniques or other low volume methods.

The term "plant" as used herein includes seedlings, bushes and trees.Furthermore, the fungicidal method of the invention includespreventative, protectant, prophylactic and eradicant treatment.

The compounds are preferably used for agricultural and horticulturalpurposes in the form of a composition. The type of composition used inany instance will depend upon the particular purpose envisaged.

The compositions may be in the form of dustable powders or graulescomprising the active ingredient (invention compound) and a soliddiluent or carrier, for example fillers such as kaolin, bentonite,kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia,Fuller's earth, gypsum, diatomaceous earth and China clay. Such granulescan be preformed granules suitable for application to the soil withoutfurther treatment. These granules can be made either by impregnatingpellets of filler with the active ingredient or by pelleting a mixtureof the active ingredient and powdered filler. Compositions for dressingseed may include an agent (for example a mineral oil) for assisting theadhesion of the composition to the seed; alternatively the activeingredient can be formulated for seed dressing purposes using an organicsolvent (for example N-methylpyrrolidone, propylene glycol ordimethylformamide). The compositions may also be in the form of wettablepowders or water dispersible granules comprising wetting or dispersingagents to facilitate the dispersion in liquids. The powders and granulesmay also contain fillers and suspending agents.

Emulsifiable concentrates or emulsions may be prepared by dissolving theactive ingredient in an organic solvent optionally containing a wettingor emulsifying agent and then adding the mixture to water which may alsocontain a wetting or emulsifying agent. Suitable organic solvents arearomatic solvents such as alkylbenzenes and alkylnaphthalenes, ketonessuch as isophorone, cyclohexanone, and methylcyclohexanone, chlorinatedhydrocarbons such as chlorobenzene and trichlorethane, and alcohols suchas benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.

Suspension concentrates of largely insoluble solids may be prepared byball or bead milling wit a dispersing agent and including a suspendingagent to stop the solid settling.

Compositions to be used as sprays may be in the form of aerosols whereinthe formulation is held in a container under pressure in the presence ofa propellant, eg. fluorotrichloromethane or dichlorodifluoromethane.

The invention compound may be mixedin the dry state with a pyrotechnicmixture to form a composition suitable for generating in enclosed spacesa smoke containing the compounds.

Alternatively, the compounds may be used in a microencapsulated form.They may also be formulated in biodegradable polymeric formulations toobtain a slow, controlled release of the active substance.

By including suitable additives, for example additives for improving thedistribution, adhesive power and resistance to rain on treated surfaces,the different compositions can be better adapted for various utilities.

The invention compounds can be used as mixtures with fertilisers (eg.nitrogen-, potassium- or phosphorus-containing fertilisers).Compositions comprising only granules of fertiliser incorporating, forexample coated with, the compound are preferred. Such granules suitablycontain up to 25% by weight of the compound. The invention thereforealso provides a fertiliser composition comprising a fertiliser and thecompound of general formula (I) or a salt or metal complex thereof.

Wettable powders, emulsifiable concentrates and suspension concentrateswill normally contain surfactants eg. a wetting agent, dispersing agent,emulsifying agent or suspending agent. These agents can be cationic,anionic or non-ionic agents.

Suitable cationic agents are quaternary ammonium compounds, for examplecetyltrimethylammonium bromide. Suitable anionic agents are soaps, saltsof aliphatic monoesters of sulphuric acid (for example sodium laurylsulphate), and salts of sulphonated aromatic compounds (for examplesodium dodecylbenzenesulphonate, sodium, calcium or ammoniumlignosulphonate, butylnaphthalene sulphonate, and a mixture of sodiumdiisopropyl- and triisopropylnaphthalene sulphonates).

Suitable non-ionic agents are the condensation products of ethyleneoxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkylphenols such as octyl- or nonyl-phenol and octylcresol. Other non-ionicagents are the partial esters derived from long chain fatty acids andhexitol anhydrides, the condensation products of the said partial esterswith ehylene oxide, and the lecithins. Suitable suspending agents arehydrophilic colloids (for example polyvinylpyrrolidone and sodiumcarboxymethylcellulose), and swelling clays such as bentonite orattapulgite.

Compositions for use as aqueous dispersions or emulsions are generallysupplied in the form of a concentrate containing a high proportion ofthe active ingredient, the concentrate being diluted with water beforeuse. These concentrates should preferably be able to withstand storagefor prolonged periods and after such storage be capable of dilution withwater in order to form aqueous preparations which remain homogeneous fora sufficient time to enable them to be applied by conventional sprayequipment. The concentrates may conveniently contain up to 95%, suitably10-85%, for example 25-60%, by weight of the active ingredient. Afterdilution to form aqueous preparations, such preparations may containvarying amounts of the active ingredient depending upon the intendedpurpose, but an aqueous preparation containing 0.0005% or 0.01% to 10%by weight of active ingredient may be used.

The compositions of this invention may contain other compounds havingbiological activity, eg. compounds having similar or complementaryfungicidal activity or which plant possess plant growth regulating,herbicidal or insecticidal activity.

A fungicidal compound which may be present in the composition of theinvention may be one which is capable of combating ear diseases ofcereals (eg. wheat) such as Septoria, Gibberella and Helminthosporiumspp., seed and soil-borne diseases and downy and powdery mildews ongrapes and powdery mildew and scab on apple etc. By including anotherfungicide, the composition can have a broader spectrum of activity thanthe compound of general formula (I) alone. Further the other fungicidecan have a synergistic effect on the fungicidal activity of the compoundof general formula (I). Examples of fungicidal compounds which may beincluded in the composition of the invention are carbendazim, benomyl,thiophanate-methyl, thiabendazole, fuberidazole, etridazole,dichlofluanid, cymoxanil, oxadixyl, ofurace, metalazyl, furalaxyl,benalaxyl, fosetyl-aluminum, fenarimol, iprodione, prothiocarb,procymidone, vinclozolin, penconazole, myclobutanil, propamocarb,R0151297, diniconazole, pyazophos, ethirimol, ditalimfos, tridemorph,triforine, nuarimol, triazbutyl, guazatine, triacetate salt of1,1'-iminodi-(octamethylene)diguanidine, buthiobate, propiconazole,prochloraz, flutriafol, hexaconazole, (2RS,3RS)-2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,(RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol,DPX H6573(1-(bis-4-fluorophenyl)methylsilyl)methyl)-1H-1,2,4-triazole,triadimefon, triademenol, diclobutrazol, fenpropimorph, pyrifenox,fenpropidin, chlorozolinate, imazalil, fenfuram, carboxin, oxycarboxin,methfuroxam, dodemorph, BAS 454, blasticidin S, kasugamycin, edifenphos,Kitazin P, cycloheximide, phthalide, probenazole, isoprothiolane,tricyclazole, 4-chloro-N-(cyano(ethoxy)methyl)benzamide, pyroquilon,chlorbenzthiazone, neoasozin, polyoxin D, validamycin A, mepronil,flutolanil, pencyuron, diclomezine, phenazin oxide, nickeldimethyldithiocarbamate, techlofthalam, bitertanol, bupirimate,etaconazole, hydroxyisoxazole, streptomycin, cyprofuram, biloxazol,quinomethionate, dimethirimol, 1-(2-cyano-2-methoxyiminoacetyl)-3-ethylurea, fenapanil, tolclofosmethyl, pyroxyfur, polyram, maneb, mancozeb,captafol, chlorothalonil, anilazine thiram, captan, folpet, zineb,propineb, sulphur, dinocap, dichlone, chloroneb, binapacryl,nitrothalisopropyl, dodine, dithianon, fentin hydroxide, fentin acetate,tecnazene, quintozene, dicloran, copper containing compounds such ascopper oxychloride, copper sulphate and Bordeaux mixture, andorganomercury compounds.

The compounds of general formula (I) can be mixed with soil, peat orother rooting media for the protection of plants against seed-borne,soil-borne or foliar fungal diseases.

Suitable insecticides which may be incorporated in the composition ofthe invention include pirimicarb, dimethoate, demeton-s-methyl,formothion, carbaryl, isoprocarb, XMC, BPMC, carbofuran, carbosulfan,diazinon, fenthion, fenitrothion, phenthoate, chlorpyrifos, isoxathion,propaphos, monocrotophas, buprofezin, ethroproxyfen and cycloprothrin.

Plant growth regulating compounds are compounds which control weeds orseedhead formation, or selectively control the growth of less desirableplants (eg. grasses).

Examples of suitable plant growth regulating compounds for use with theinvention compounds are the gibberellins (eg. GA₃, GA₄ or GA₇), theauxins (eg. indoleacetic acid, indolebutyric acid, naphthoxyacetic acidor naphthylacetic acid), the cytokinins (eg. kinetin, diphenylurea,benzimidazole, benzyladenine or benzylaminopurine), phenoxyacetic acids(eg. 2,4-D or MCPA), substitued benzoic acid (eg. triiodobenzoic acid),morphactins (eg. chlorfluoroecol), maleic hydrazide, glyphosate,glyphosine, long chain fatty alcohols and acids, dikegulac,paclobutrazol, fluoridamid, mefluidide, substituted quaternary ammoniumand phosphonium compounds (eg. chloromequat chlorphonium ormepiquatchloride), ethephon, carbetamide, methyl-3,6-dichloroanisate,daminozide, asulan, abscisic acid, isopyrimol,

The following Examples illustrate the invention. Throughout theseExamples, the term `ether` refers to diethyl ether; chromatography wascarried out using silica gel as the solid phase; magnesium sulphate wasused to dry solutions; and reactions involving water- or air-sensitiveintermediates were performed under atmospheres of nitrogen. Temperaturesare expressed in degrees centigrade.

Where shown, infrared and nmr data are selective; no attempt is made tolist every absorption. The following abbreviations are used throughout:

    ______________________________________                                        DMF =  .sub.--N, .sub.--N-dimethylformamide                                   g = gramme(s)      delta = chemical shift                                     mmol = millimole(s)                                                                              CDCl.sub.3 = deuterochloroform                             ml = milliliter(s) s = singlet                                                mmHg = millimetres pressure                                                                      d = doublet                                                of mercury         t = triplet                                                M.P. = melting point                                                                             br = broad                                                 nmr = nuclear magnetic resonance                                              ______________________________________                                    

EXAMPLE 1

This Example illustrates the preparation of E-methyl2-[2'-(6"-chloropyrazin-2"-yloxy)phenyl]-3-methoxypropenoate (CompoundNo. 2 of Table I).

2-Hydroxyphenylacetic acid (50 g) was added to a solution of hydrogenchloride in methanol [prepared from acetyl chloride (25 ml) and methanol(250 ml)]. The solution was stirred at room temperature for three hoursand then allowed to stand overnight (fifteen hours). The resultingmixture was concentrated under reduced pressure, and the residue wastaken up in ether (250 ml) and washed with an aqueous solution of sodiumbicarbonate until effervescence ceased. The ethereal solution was driedand then concentrated under reduced pressure and the resulting solid wasrecrystallized from ether/petrol to afford methyl 2-hydroxyphenylacetate(50 g; 92% YIELD) as white, powdery crystals, M.P. 70°-72° C.; infraredmaxima (nujol mull): 3420, 1715 cm⁻¹ ; ¹ H nmr (CDCl₃, 90 MHz): delta3.70 (2H, s), 3.75 (3H, s), 6.80-6.95 (2H, m), 7.05-7.10 (1H, m),7.15-7.25 (1H, m), 7.40 (1H, s) ppm.

Methyl 2-hydroxyphenylacetate (21.0 g) was dissolved in dry DMF (200ml), and dry potassium carbonate (19.35 g) was added in one portion.Benzyl bromide (23.94 g) in dry DMF (50 ml) was added dropwise to thismixture, with stirring, at room temperature. After eighteen hours themixture was poured into water (500 ml) and extracted with ether (2×400ml). The extracts were washed with water (3×150 ml) and brine (100 ml),dried and filtered through silica gel (50 g; Merck 60), thenconcentrated under reduced pressure to afford a yellow oil. Distillationat 160° C. and 0.05 mmHg afforded methyl 2-benzyloxyphenylacetate as aclear, colourless oil (26.99 g; 83% yield), infrared maximum (film):1730 cm⁻¹ ; ¹ H nmr (CDCl₃, 90 MHz): delta 3.60 (3H, s), 3.75 (2H, s),4.10 (2H, s), 6.80-7.40 (9H, m) ppm.

Methyl 2-benzyloxyphenylacetate (26.99 g) and methyl formate (126.62 g)in dry DMF (300 ml) were added dropwise to a stirred suspension ofsodium hydride (50% disp. in oil, 10.13 g) in DMF (300 ml) at 0° C.After stirring at 0° C. for two hours the mixture was poured into water(1000 ml) and washed with ether (2×150 ml). The aqueous layer wasacidified to pH4 with 6M hydrochloric acid then extracted with ether(2×350 ml). The extracts were dried and concentrated under reducedpressure to afford crude methyl3-hydroxy-2-[2'-benzyloxyphenyl]propenoate as a yellow oil, infraredmaxima (film): 1720, 1660 cm⁻¹.

The crude methyl 3-hydroxy-2-(2'-benzyloxyphenyl)propenoate wasdissolved in dry DMF (100 ml) and potassium carbonate (29.0 g) was addedin one portion. Dimethyl sulphate (16.00 g) in dry DMF (10 ml) was thenadded dropwise with stirring. After ninety minutes, water (300 ml) wasadded and the solution was extracted with ether (2×300 ml). Afterwashing with water (3×150 ml) and brine, the extracts were dried andconcentrated under reduced pressure, and the resulting yellow oilsolidified on trituation with ether/petrol. Recrystallization from drymethanol afforded E-methyl 3-methoxy-2-(2'-benzyloxyphenyl)propenoate asa white, crystalline solid (5.44 g, 17% yield from methyl2-bemnzyloxyphenylacetate), M.P. 76°-77° C.; infrared maxima (nujolmull): 1710, 1640 cm⁻¹ ; ¹ H nmr (CDCl₃, 90 MHz): delta 3.63 (3H, s),3.75 (3H, s), 5.05 (2H, s), 6.80-7.40 (9H, m), 7.50 (1H, s) ppm.

E-methyl 3-methoxy(2'-benzyloxyphenyl)propenoate (5.44 g) was dissolvedin ethyl acetate (50 ml) and 5% palladium on carbon (0.25 g) was added.The stirred mixture was hydrogenated at three atmospheres pressure, withstirring, until no more hydrogen was taken up, then filtered throughcelite and silica gel (50 g, Merck 60). Concentration of the filtrateunder reduced pressure afforded E-methyl3-methoxy-2-(2'-hydroxyphenyl)propenoate as a white crystalline solid(3.76 g; 99% yield), M.P. 125°-126° C.; infrared maxima (nujol mull):3400, 1670 cm⁻ ; ¹ H nmr (CDCl₃, 270 MHz): delta 3.80 (3H, s), 3.90 (3H,s), 6.20 (1H, s), 6.80-7.00 (2H, m), 7.10-7.30 (2H, m), 7.60 (1H, s)ppm.

E-Methyl 3-methoxy-2-(2'-hydroxyphenyl)propenoate (0.5 g) and2,6-dichloropyrazine (1.79 g) were dissolved in dry DMF (10 ml) and thensodium hydride (0.24 g, 50% dipersion in oil) was added in portions.After stirring for 30 minutes, water was added dropwise. The reactionmixture was then poured into water (50 ml) and extracted with ether(2×100 ml). The ether layers were combined, washed with water (3×100 ml)and brine (50 ml) and then dried and filtered. Removal of the solventunder reduced pressure afforded a yellow oil which was purified bychromatography on silica gel (eluent ether) to give the title compoundas a viscous yellow oil (75 mg); ¹ H nmr (CDCl₃): delta 3.75 (3H, s),3.80 (3H, s), 7.50 (1H, s), 8.20 (1H, s), 8.30 (1H, s) ppm.

EXAMPLE 2

This Example illustrates the preparation of E-methyl3-methoxy-2-[2'-(4"-chloro-6"-methoxy-S-triazin-2"-yloxy]propenoate(compound No. 72 of Table 1).

A solution of E-methyl 3-methoxy-2-(2'-hydroxyphenyl)propenoate (0.61 g,prepared as in Example 1) in acetone (20 ml) was stirred with anhydrouspotassium carbonate (0.20 g) at room temperature for 45 minutes and then2,4-dichloro-6-methoxy-S-triazine (0.48 g) was added. After 2 days water(13 ml) was added to the stirred mixture and after a further 1 hour thereaction mixture was diluted with water and extracted with ether (2x).The extracts were dried and concentrated under reduced pressure to givea pale yellow oil which crystallised on standing. Recrystallisation fromcyclohexane afforded the title compound as a white crystalline solid(0.33 g), m.pt. 121°-123° C.; ¹ H NMR (CDCl₃, 90 MHz); delta 3.61 (3H,s); 3.75 (3H, s); 3.95 (3H, s); 7.1-7.4 (4H, m); 7.45 (1H, s) ppm.

EXAMPLE 3

This Example illustrates the preparation of E-methyl3-methoxy-2-[2'-(4",6"-dichloro-S-triazin-2"-yloxy)phenyl]propenoate(Compound No. 29 of Table 1).

A solution of E-methyl 3-methoxy-2-(2'-hydroxyphenyl)propenoate (2.08 g,prepared as in Example 1) in acetone (70 ml) was stirred with potassiumcarbonate (0.69 g) at 0.20 -5° C. 2,4,6-Trichloro-S-triazine (1.85 g)and water (45 ml) were added and the mixture stirred vigorously for 3.5hours at 0°-5° C. The reaction mixture was then diluted with water andextracted with ether. The extract was washed with dilute aqueous sodiumhydroxide (2x) and water and then dried. Removal of the solvent underreduced pressure left a pale yellow solid residue which was purified byblack chromatography (silica gel, petroleum ether-ether) to give thetitle compound as a white crystalline solid (0.16 g), m.pt. 141°-142.5°C.; ¹ H NMR (CDCl₃, 90 MHz); delta 3.62 (3H, s); 3.77 (3H, s); 7.1-7.5(4H, m); 7.46 (1H, s) ppm.

The following are examples of compositions suitable for agricultural andhorticultural purposes which can be formulated from the compounds of theinvention. Such compositions form another aspect of the invention.Percentages are by weight.

EXAMPLE 4

An emulsifiable concentrate is made up by mixing and stirring theingredients until all are dissolved.

    ______________________________________                                        Compound No. 2 of Table I                                                                            10%                                                    Benzyl alcohol         30%                                                    Calcium dodecylbenzenesulphonate                                                                      5%                                                    Nonylphenolethoxylate (13 moles                                                                      10%                                                    ethylene oxide)                                                               Alkyl benzenes         45%                                                    ______________________________________                                    

EXAMPLE 5

The active ingredient is dissolved in methylene dichloride and theresultant liquid sprayed on to the granules of attapulgite clay. Thesolvent is then allowed to evaporate to produce a granular composition.

    ______________________________________                                        Compound No. 2 of Table I                                                                           5%                                                      Attapulgite granules 95%                                                      ______________________________________                                    

EXAMPLE 6

A composition suitable for use as a seed dressing is prepared bygrinding and mixing the three ingredients.

    ______________________________________                                        Compound No. 2 of Table I                                                                          50%                                                      Mineral oil           2%                                                      China clay           48%                                                      ______________________________________                                    

EXAMPLE 7

A dustable powder is prepared by grinding and mixing the activeingredient with talc.

    ______________________________________                                        Compound No. 2 of Table I                                                                           5%                                                      Talc                 95%                                                      ______________________________________                                    

EXAMPLE 8

A suspension concentrate is prepared by ball milling the ingredients toform an aqueous suspension of the ground mixture with water.

    ______________________________________                                        Compound No. 2 of Table I                                                                          40%                                                      Sodium lignosulphonate                                                                             10%                                                      Bentonite clay        1%                                                      Water                49%                                                      ______________________________________                                    

This formulation can be used as a spray by diluting into water orapplied directly to seed.

EXAMPLE 9

A wettable powder formulation is made by mixing together and grindingthe ingredients until all are thoroughly mixed.

    ______________________________________                                        Compound No. 2 of Table I                                                                          25%                                                      Sodium lauryl sulphate                                                                              2%                                                      Sodium lignosulphonate                                                                              5%                                                      Silica               25%                                                      China clay           43%                                                      ______________________________________                                    

EXAMPLE 10

Compounds 2, 29 and 72 of Table I were tested against a variety offoliar fungal diseases of plants. The technique employed was as follows.

The plants were grown in John Innes Potting Compost (No. 1 or 2) in 4 cmdiameter minipots. The test compounds were formulated either by beadmilling with aqueous Dispersol T or as a solution in acetone oracetone/ethanol which was diluted to the required concentrationimmediately before use. For the foliage diseases, the formulations (100ppm active ingredient) were sprayed onto the foliage and applied to theroots of the plants in the soil. The sprays were applied to maximumretention and the root drenches to a final concentration equivalent toapproximately 40 ppm a.i./dry soil. Tween 20, to give a finalconcentration of 0.05%, was added when the sprays were applied tocereals.

For most of the tests the compound was applied to the soil (roots) andto the foliage (by spraying) one or two days before the plant wasinoculated with the disease. An exception was the test on Erisiphegraminis in which the plants were inoculated 24 hours before treatment.Foliar pathogens were applied by spray as spore suspensions onto theleaves of test plants. After inoculation, the plants were put into anappropriate environment to allow infection to proceed and then incubateduntil the disease was ready for assessment. The period betweeninoculation and assessment varied from four to fourteen days accordingto the disease and environment.

The disease control was recorded by the following grading:

4=no disease

3=trace -5% of disease on untreated plants

2=6-25% of disease on untreated plants

1=26-59% of disease on untreated plants

0=60-100% of disease on untreated plants

The results are shown in Table II.

                                      TABLE II                                    __________________________________________________________________________    COM-                         PYRICU-                                          POUND PUCCINIA                                                                              ERYSIPHE                                                                             VENTURIA                                                                              LARIA CERCOSPORA                                                                              PLASMOPARA                                                                            PHYTOPHTHORA             NO.   RECONDITA                                                                             GRAMINIS                                                                             INAEQUALIS                                                                            ORYZAE                                                                              ARACHIDICOLA                                                                            VITICOLA                                                                              INFESTANS                (TABLE I)                                                                           (WHEAT) (BARLEY)                                                                             (APPLE) (RICE)                                                                              (PEANUTS) (VINES) (TOMATO)                 __________________________________________________________________________    2     4       4      4       4     4         4       3                        29    --      0      --      3     --        4       0                        72    0       0      2       0     --        4       3                        __________________________________________________________________________     -- Not tested                                                            

We claim:
 1. A compound having the formula (I): ##STR79## andstereoisomers thereof, wherein X, Y and Z, which are the same ordifferent, are hydrogen, halogen, hydroxy, C₁₋₆ alkyl, C₂₋₆ alkenyloptionally substituted with phenyl, furyl, thienyl or pyridyl, phenyl,C₂₋₆ alkynyl optionally substituted with phenyl, C₁₋₆ alkoxy, phenoxy,phenyl(C₁₋₆)alkyl, phenyl(C₁₋₆)alkoxy, phenoxy(C₁₋₆)alkyl, C₁₋₆alkanoyl, benzoyl, amino, C₁₋₆ alkanoylamino, benzoylamino, furoylamino,thienylcarbonylamino, nitro, cyano, --CO₂ R¹, --CONR² R³ or --COR⁴, thealkyl moieties of any of the foregoing groups being optionallysubstituted with hydroxy, halogen, C₁₋₄ alkoxy orC₁₋₄ alkoxycarbonyl,the phenyl or heterocyclic moieties of any of the foregoing groups beingoptionally substituted with one or more of halogen, hydroxy, C₁₋₄ alkyl,C₁₋₄ alkoxy, trifluoromethyl, trifluoromethoxy, phenoxy, benzyloxy,nitro, amino, phenyl, carboxy, C₁₋₆ alkoxycarbonyl, cyano, C₁₋₆alkylcarbonylamino or methylenedioxy and any of the foregoing aminomoieties being optionally substituted with N-phenyl or N--C₁₋₆ alkyl; Wis a C-linked pyrazinyl ring optionally substituted withhalogen, nitro,C₁₋₄ alkyl which is itself optionally substituted withhalogen, hydroxyor C₁₋₄ alkoxy, C₁₋₄ alkoxy which is itself optionally substitutedwithhalogen, hydroxy or C₁₋₄ alkoxy, phenoxy which is itself optionallysubstituted withhalogen, hydroxy, amino which is itself optionallysubstituted withC₁₋₄ alkyl, or cyano, or W is benzopyrazin-2-yl; A isoxygen or sulphur; and R¹, R², R³, and R⁴, which are the same ordifferent, are hydrogen, C₁₋₆ alkyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₆)alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, phenyl orphenyl(C₁₋₆)alkyl, in which the phenyl moieties are optionallysubstituted as defined above.
 2. A compound according to claim 1 whereinX, Y and Z which are the same or different, are hydrogen, fluoro,chloro, bromo, hydroxy, methyl, methoxy trifluoromethyl, methylamino ordimethylamino.
 3. A compound according to claim 1 which is in the formof the (E)-isomer.
 4. A compound according to claim 2 in which X, Y, andZ are all hydrogen.
 5. A fungicidal composition comprising, as an activeingredient, a fungicidally effective amount of a compound according toclaim 1 together with a fungicidally acceptable carrier or diluenttherefor.
 6. A method of combating fungi which comprises applying to aplant, to seed of a plant, or to a locus of the plant or seed, aneffective amount of a compound as claimed in claim 1.